The aim of the study is to study the profile of ethanol and non-oxidative biomarkers (ethyl glucuronide, ethyl sulphate and fatty acid ethyl esters) after experimental administration of increasing doses of alcohol in adult subjects.
The abuse of alcohol causes serious health and social problems. Alcohol consumption can be monitored by detecting biomarkers. In current practice indirect biomarkers (mean corpuscular volume, transaminases, gammaglutamyl or carbohydrate-deficient transferrin) are used, although direct biomarkers of alcohol, including alcohol itself and metabolites also exist. Biomarkers of alcohol consumption are used as tools to prevent health and social problems related with alcohol, allowing the identification of subjects at risk of abuse, dependence or withdrawal and to assess the efficacy of treatments for alcohol dependence. Non-oxidative metabolites (ethyl glucuronide, ethyl sulphate and fatty acid ethyl esters) have longer biological half-life than ethanol and accumulate in tissues after consumption. The objective of the study is to study the profile of ethanol and non-oxidative biomarkers (ethyl glucuronide, ethyl sulphate and fatty acid ethyl esters) after experimental administration of increasing doses of alcohol in adult subjects. Subjects will be genotyped for genetic polymorphisms of proteins related to ethanol metabolism and effects (as alcohol dehydrogenase and aldehyde dehydrogenase), and the genotypes will be used to evaluate their influence in the results.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
54
Alcohol single oral dose
Alcohol single oral dose
Alcohol single oral dose
Parc de Salut Mar (IMIM)
Barcelona, Barcelona, Spain
Area Under the Concentration-Time Curve (AUC 0-24h)
Calculation of the AUC for plasma fatty acid ethyl esters (palmitic, stearic, linoleic and oleic acid ethyl esters) concentrations. Blood samples will be obtained baseline and at 0,25, 0,50, 0,75,1, 1,25, 1,50, 1,75, 2, 2,5, 3, 3,5, 4, 5, 6, 8, 10, 24h. Additional samples will be collect at 72 h and 1 week, 1 and 2 months after administration. At 3 months a sample will be obtained in selected participants.
Time frame: From baseline to 24 hours after administration
Area Under the Concentration-Time Curve (AUC 0-24h)
Calculation of the AUC for plasma and saliva concentrations of ethanol and its non-oxidative metabolites ethyl sulphate and ethyl glucoronide. Blood samples will be obtained baseline and at 0,25, 0,50, 0,75,1, 1,25, 1,50, 1,75, 2, 2,5, 3, 3,5, 4, 5, 6, 8, 10, 24. Additional samples will be collected at 72 h and 1 week, 1 month and 2 months after administration. At 3 months a sample in selected participants. Saliva samples at baseline and 0,5, 1, 2, 3, 4, 6, 10 and 24 h after administration
Time frame: From baseline to 24 hours after administration
Cumulative amount of drug excreted into urine up to collection time of last measurable concentration
Urine will be collected in the following intervals 0-6h, 6-12h, 12-24h, 24-48h, 48-72h and the total amount of ethanol and its non-oxidative metabolites ethyl sulphate and ethyl glucoronide will be calculated.
Time frame: From baseline to 72 hours after administration
Elimination half-life
Calculation of elimination half-life from ethanol and its non-oxidative metabolites (fatty acid ethyl esters, ethyl sulphate and ethyl glucoronide) concentrations in plasma
Time frame: From baseline to 24 hours after administration
Fatty acid ethyl esters and ethyl glucoronide hair concentrations
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Alcohol single oral dose
Alcohol single oral dose
Concentrations of fatty acid ethyl esters and ethyl glucoronide in hair at baseline, one and two month after administration. An additional sample at 3 months in selected participants.
Time frame: Baseline, 1 and 2 months after administration
Change in subjective effects of ethanol
Participants will self-report their experience on a visual analogue scale of drunkenness and Biphasic alcohol effects scale (BAES) at baseline and 0.5,0.75,1,1.5,2,4,6,8,10 after administration.
Time frame: From baseline to 10 hours after administration
Number of Participants with Serious and Non-Serious Adverse Events
Collection of adverse effects spontaneously reported by the participants and/or observed by the investigators
Time frame: From baseline to 24 hours after administration
Change in Addiction Research Center Inventory (ARCI)
ARCI will be administered baseline and 10 h after administration (subjects should answer at 10 h remembering their experience at the moment of maximum effects)
Time frame: From baseline to 10 h after administration
Change in Evaluation of Subjective Effects of Substances with Abuse Potential (VESSPA)
VESSPA will be administered baseline and 10 h after administration (subjects should answer at 10 h remembering their experience at the moment of maximum effects)
Time frame: From baseline to 10 h after administration
Ethanol dose identification questionaire
Participants should guess the dose they have ingested during the experimental session among 5 options (10, 20, 40, 60 and 80 g of ethanol)
Time frame: 10 h after administration
Urinary drug concentrations
Urinary concentrations of ethanol and its non-oxidative metabolites ethyl sulphate and ethyl glucoronide will measured at 1 week, 1 and 2 months after administration (3 months in selected subjects)
Time frame: From 1 week to 2 months